Ars Medendi reads: The Man Who Mistook His Wife for a Hat

The Book

The Man Who Mistook His Wife for a Hat

Oliver Sacks

Picador, 1986

What it’s about: A Summary

Welcome to the world of a neurologist. Oliver Sacks compiles many case studies he has published in medical case journals. These serve both as incredibly insightful looks at particular neurological disorders.

This is the only one of Sacks’ books I have read, but it is the most iconic. And it is worth a read for anyone interested in the subject area. In fact, I would recommend it as a window into the personal nature medicine takes on especially in matters of the brain, our most misunderstood organ.

The Review:

“Constantly my patients drive me to question, and constantly my questions drive me to patients – thus in the stories or studies which follow there is a continual movement from one to the other.”

Throughout the book, Sacks refers to Luria’s neurological case work, and he uses his extensive knowledge to craft the cases, peppering them with appropriate quotations and scientific context. And yet throughout, the patients are depicted as profoundly human and deeply sympathetic. It is these patients that lie at the centre of the book, and at the centre of Sacks’ life.

Oliver Sacks’ book is varied by the different tales in it. Therefore it stands to reason that a review should look into each section separately.

Losses

This section of the book encompasses the deficits, or the “A”s – Aphasia, Ataxia, Agnosia etc. It is this section which includes the iconic “The Man Who Mistook His Wife for a Hat” – the true story of a man unable to visually process shapes and assign them with identify. It is for this reason that, during his interview with Sacks, he “took hold of his wife’s head and tried to put it on”. This section of the book explores the impact of memory disorders. Another story “The Lost Mariner” describes a man trapped in his past, unable to form new memories or understand his present.

Excesses

This section is perhaps the opposite to Losses, comprising of manias and hyper-activities of the brain such as Tourette’s. Striking is the story of one man plagued with the latter (“Witty, Ticcy Ray”), wherein the patient decides that he will only undergo treatment by Haldol for his condition on certain days of the week. It is in this way that we can understand how intrinsic the workings of the brain are to a person’s personality and creative ability; such that, perhaps, we cannot treat the former without affecting the latter to a degree.

Transports

This section is exactly as it sounds. Stories of patients transported elsewhere by their brains. “A Passage to India” is a story of an Indian girl with a malignant tumour that expanded to compress areas of her brain. It is at once a melancholic and beautiful tale. In a way, her visions of India were her salvation from an impossible prognosis, as understood fully only by her: “I like these dreams – they take me back home.”

The World of the Simple

It is this section that explores the world of the “autistic savant”: those dismissed due to their placement on the autistic spectrum, but who have intense creative or mathematical talents. “A Walking Grove” is the story of a man with severe developmental deficiencies able to ”retain an opera or an oratorio on a single hearing”. Is it through these abilities that he develops with relationship with his musical father, despite being unable to express himself through other means.

Bottom line: if any of these cases sounds interesting to you, I highly recommend picking up this book. It is truly extraordinary.

 

A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 14 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

Ars Medendi reads: The Noonday Demon

The Book

The Noonday Demon – An Atlas of Depression

Andrew Solomon

Scribner, 2003

What it’s about: A Summary

First of all, I have to say: the book is LONG. Very long. It took me maybe two months to read, but then I don’t have much time to read in the evenings after work. Despite it’s length, I highly recommend it.

As suggested in the title the book is an entire atlas of the disorder: providing insight into all relevant areas of context from a personal to a society-wide level. What the title doesn’t tell is how beautifully written it is.: “In depression, the meaninglessness of life itself, becomes self-evident. The only feeling left in this loveless state is insignificant”.

I would recommend a read for anyone suffering from depression, or interested in the disorder.

On the author

Andrew Solomon is a journalist, and this is evident from the sheer volume of research and detail going into the book. In the book, he often brings in his own experience into the writing, laying bear his vulnerabilities and the devastation depression has wrought to his life.

The Review:

“My depression has grown on me as that vine had conquered the oak; it had been a sucking thing that has wrapped around me, ugly and more alive than I. It had had a life of its own that bit by bit asphyxiated all of my life out of me.”

The strength and power of The Noonday Demon lies with the dozens of stories that feed into it. Each is the story of an individual, but they together give valuable insight into the understanding of one of the world’s most prevalent diseases.

Although the author admits he is not a scientific expert of any kind, his dedication to studying depression is shown through his detailed exploration of the disorder from its historical, cultural and political roots, to its chemical pathways and various treatments. And, as I mentioned before, the writing is at once compelling and stunning. The story of the author is interwoven with an exploration of all the aspects of our modern day (and historical context) that cause so many to suffer from depression.

In Breakdowns, the author explains the debilitating acute condition, and it is a powerful read. The author then goes on to describe talking therapies (those which come out of traditional psychoanalysis and are subscribed to by psychiatrists) and the physical interventions (from psychopharmacological therapies to harsher therapies such as electroshock therapy).

Both types rely on restoring a “normal” balance to the patient, both in encouraging positive thought and constructive action, and in restoring chemical balance. And both are personalised to the idiosyncratic patient’s needs, and must work together. In particular, antidepressants are chosen primarily based on their side-effects, something which is at once paradoxical and essential as many are incredibly unpleasant even now: “you take antidepressants like you take radiation for cancer.” Solomon also does not avoid discussing alternative medicines. This is particularly important due to the tendency to hail Prozac or nothing, despite the availability of alternative therapies of all types.

The next sections describe the various aspects of a person’s life experience that can lead to the depressive condition. It is in these sections that the stories of depressives truly shine and make the reader understand the importance of different cultural prejudices, addictions and poverty. He does not overdramatize or sweep these issues under the Prozac blanket as is so often tempting in the media. And yet he depicts the cycle of depression experienced by all too many people in our society.

Overall this is an honest, stark text depicting the often under-represented truths about depression as well as those we have heard often. Aptly, the final chapter is simply title Hope.

“Some people suffer mild depression and are totally disabled by it’ others suffer severe depression and make something of their lives anyway.” It is hope that makes the difference.

 

A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 14 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

Ars Medendi reads: The Man Who Couldn’t Stop

I have absolutely no illusions about this blog, and I am fully aware that the majority of the time I’m talking to myself. So I thought it would be worthwhile starting a new feature where I review books I have read. If you are reading this and have yourself read the book I am reviewing, I’d love to hear your thoughts!

 

The Book

The Man Who Couldn’t Stop

David Adam

Picador, 2014

 

What it’s about: A Summary

Broadly speaking, the book is the personal story of our author’s struggle with Obsessive Compulsive Disorder (OCD), interspersed with vital information on the historical, political and medical context of the disease. I adored this book.

It gives a slice of life into the struggles of an OCD sufferer, whilst educating you in an fascinating way that shows you it is more than just a “behavioural quirk”. The straightforward way in which the author reveals his deepest, darkest obsessions is both compelling and incredibly insightful for someone who has never truly understood the disorder before.

It is separated into different sections, each providing a different context for the development of the modern disease model and treatment. The writing style is also of note for its scientific and yet personal nature.

 

On the author

David Adam is a writer and editor of the journal Nature. That he was a correspondent for The Guardian whilst in the thralls of his disorder speaks volumes for his bravery.

 

The Review:

“An Ethiopian schoolgirl names Bira once ate a wall of her house… By the time she was 17 years old she had eaten eight square metres of the wall – more than half a tonne of mud bricks.”

It is hard to explain a mental disorder to one who has not studied medicine, and yet, from this book, I feel as though I have seen through the eyes of a person with OCD. At times hard to read and at others impossible to put down, I found that the take home message was simply that of enlightenment. Enlightening readers that no one is “a little bit OCD”; but that OCD is a serious condition that is frustratingly, and painfully, hard to treat (consider the famous “white bear” experiment referenced throughout this book).

In terms of historical context, the existence of OCD in the religious community, the animal world, and the difficulty of its treatment even up to the current day are explored. The grisly chapter on lobotomies is particularly striking, with almost unbelievable tales of “brains irreversibly damaged by cavalier surgeons armed with nothing more precise than knitting needles”.

These contextual sections at times descend into an Oliver Sacks-like description of patient cases, which is incredibly compelling (amongst the more well-known being Phineas Gage and the Collyer brothers). Also of note is the amusing use of paradoxical Freudian psychoanalyses, encouraging OCD sufferers to obsess more deeply into their intrusive thought, as a more “successful” early treatment.

The book also chronicles evolutions of diagnosis, and how it is essential that we consider such psychiatric disorders on a sliding scale rather than as black-or-white diagnoses. Also key to consider is the importance of personalised medicine, and further research into the use of behavioural therapies as well as drugs to treat patients where it is not possible to pinpoint something “physically” wrong.

I recommend this book to anyone curious about OCD or any psychiatric disorder.

 

A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 14 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

Let’s have a talk about homeopathy

A note from the author: As this is an emotive subject, comments are disabled after 4 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

 

As my first post in a very, very long while, I thought I’d post an extended discussion about some aspects of homeopathy.

Homeopathy is an alternative medicine (as stated in Tim Minchin’s famous song), based on the theory that “like cures like”.(1) This means that “a substance taken in small amounts will cure the same symptoms it causes if it were taken in large amounts”.(2-5)

As I work as a research Chemist, I have to state that I am biased when it comes to alternative medicine. To me, science must be evidence-based to have value; and thus medical practice, which is based on the science, should also be inherently evidence-based. By “evidence-based, I mean there is insufficient scientific research to justify the inclusion of homeopathic method in the standard library of standard medical treatments.(4)

However, in order to fully examine the potential of this theory, I believe it is worth discussing some instances where the homeopathic approach might actually be successful. In doing so, perhaps we can find a reason for the use of alternative medicine by so many people.

 

Successes: X-rays

 

In the modern age, cancer treatment is either through the use of chemicals (chemotherapy) or radiation (radiotherapy). X-rays were discovered in 1895, soon after which scientists unlocked their use in therapeutic applications. In 1986, Emil Grubbé (a physician with training in homeopathy) assembled an x-ray machine and used it to treat a recurrent breast carcinoma.(6)

Though unsuccessful at first, Grubbé’s treatments were potentially more successful than others due to his use of lower exposures for less time, and throughout the rest of his life he taught many others his techniques. X-ray radiation therapy today actually uses a “fractionated” process where low doses are administered over a longer course of time to minimise side-effects.(7)

Homeopathic theory in the case of X-rays works because they kill cells. Therefore it stands to reason that a low dose is best to avoid killing the desired cells. Our intrepid homeopathic physician, Grubbé, unfortunately, fell foul of the damage that X-rays can do at higher exposures, and himself had to undergo many surgeries to treat recurrent cancers.

 

Successes: Hay Fever

 

As another example of homeopathic “success”, let’s look at hay fever.(8-11) The majority of people with hay fever can simply avoid the pollen that triggers it in various ways, or take anti-histamines. Those with more sever allergies may be referred to immunotherapy. Immunotherapy is a treatment where the body’s immune system is exposed gradually to increasing levels of the allergen (pollen), such that their immune cells become tolerant.

The reason to only gradually increase the dose is to minimise side-effects, but this does mean that it takes a long time to reach the point at which the patient is “cured”. At this point, they must take maintenance doses to sustain tolerance. It stands to reason, then, that exposure to allergens (at a homeopathic dose) would potentially reduce the symptoms for some hay fever-sufferers as a form of immunotherapy for those with less severe symptoms.

 

Why successful?

 

So what do these two “successes” have in common? Both are situations where the homeopathic approach happens to coincide with what we currently use in medical practice anyway. They work because exposure to X-rays kills cells, and we want that to happen in cancer treatment. Lower doses result in less peripheral cell deaths and thus less side-effects. They work because pollen induces immune cell responses. Lower doses result in less immune cell responses and thus less side-effects (and thus immune cell tolerance). These are both therapies where evidence exists for their success.

 

As Tim Minchin says, “Do you know what they call alternative medicine that’s been proved to work? Medicine.”(1) But that’s not the appeal of homeopathy.

Stripping down the theory, people like homeopathy because it is “natural”, using the same “natural” cause of a disorder to fix it. And they like it because it has few side-effects. Let’s explore these things.

 

The Unfortunate truth

 

Alas, this is where I look less optimistically into homeopathic method. This is because, as a Research Chemist, I am used to spending my days purifying chemicals and diluting them down to acceptable concentrations for use on cells or proteins. Side-effects tend to occur where the given dose of a drug has effects beyond the desirable local effects. The reason that homeopathic remedies have little to no side effects is because the doses are so low as to have no effects in the body.

Dosage

The homeopathic dilution method uses a logarithmic scale, with C being a dilution by 100 and X being a dilution by 10.(12) A 2C dilution is 1 part in 100, repeated twice (so 1 in 1002 final concentration), 6C is 1 part in 100 repeated 6 times (1 in 1006 final concentration). A 10C dilution is 1 part in 10 repeated 10 times (so 1 in 1010 final concentration) etc etc…

As I have never taken a homeopathic remedy, I had a cursory glance at some online shops to see if anything interesting popped up. I found Mercurious Chloride (Calomel, Hg2Cl2 – I will refer to it as Mercurous Chloride, it’s proper chemical name).(14) This is acutely toxic, causes respiratory sensitization and is hazardous to the aquatic environment according to Sigma-Aldrich, but that is not mentioned on homeopathy suppliers’ websites.(13-14) Not to spoil the surprise, but this is likely because of the very small quantities of active ingredients.

Let’s do some Maths. One supplier offers a pack of 160 g of tablets at 6X potency (for £22.35). 6X potency is 1 in 106 – so 0.00016 g of Calomel is in this 160g. From the shop I looked at, each tablet was approximately 0.11 g.

So, per tablet, we are looking at 0.00000011 g of the chemical. This is a tiny, tiny amount.

The amount of mercury in the water supply (determined to be a entirely safe amount that has no effect) is around 1 microgram per litre.(15) So 1 l contains 0.000001 g of the chemical: or, around ten times as much as in a homeopathic tablet. Frankly, this makes it obvious why people claim that homeopathic remedies are placebos (medicines with no therapeutic benefit).

The cost for this 0.00016 g of Mercurous Chloride is also extortionate: considering that 5 g of the pure chemical would cost less than £30, the mark up is therefore more than 2,300,000%. The numbers speak for themselves.

Natural Remedies

I’d also like to briefly step on the issue of “natural sources”. Some Mercury is purified from mined cinnabar (HgS), and this source gives the most “natural” method (the least steps) of Mercurous Chloride production:

Step 1) Cinnabar ore is heated in air and the resulting Mercury vapour is condensed and collected.

Step 2) Mercuric Chloride is formed by adding Hydrochloric acid to this elemental Mercury.

Step 3) This Mercuric Chloride is then reacted with elemental Mercury to form our Mercurous Chloride.

In the modern age, there is an increasing trend to consume “natural” food and to “detox” your body. It therefore stands to reason that people are concerned about putting potentially harmful substances in their body. I completely understand this and I subscribe to keeping a healthy diet. However, it does not apply when it comes to medicine.

Pure chemicals do not occur in nature, and thus natural remedies are not inherently more safe than those prepared in a lab. Chemical intervention is needed in every case to obtain pure substances, whether for purification or (in this case) to actually make the chemical in which we are interested. Regulated homeopathic remedies are always subject to some form of purification before they are sold on. I would be far more concerned about anything unregulated, as you cannot know whether you are consuming something harmful. If the mood calls for it, I’ll be happy to discuss the natural vs. natural debate at another time, but I have no time for it here.

 

But what’s the harm?

 

What is the harm indeed? If people are willing to spend lots of money on something that has no effect, then it is their choice.

This has been discussed before, and I don’t want to retread very well-trodden ground, so I’ll just summarise here. Individuals using homeopathic treatments instead of conventional medicine are spending more money for treatments that, more often than not, do not work.

A good book to read on this issue is “Trick of Treatment?: Alternative Medicine on Trial” by Simon Singh and Edzard Ernst. There are also other articles on the same subject such as here.

 

What can we learn from homeopathy?

 

So here’s where I go back to my original thoughts. What is the potential in homeopathy?

The inherent value of alternative therapy is that people are different. Not all people like to be told that there is one, and only one, way of curing your disease or disorder. Being treated by alternative medicine is like being part of an exclusive club, like being a medical hipster – and there are huge online communities dedicated to discussing it. These communities have their own “experts” – people who have tried homeopathic treatments and recommend them to others. Obviously people like to feel like they understand what’s going on in their own life, and health is potentially the most important aspect. And subscribing to alternative therapy is one way of regaining control.

Is it really worth it though? Homeopathy becomes most attractive where patients are at their most vulnerable. Where patients are scared to take a nasty treatment with known side-effects, or when they have no other available treatment. Homeopathy cuts through the jargon of complex medical treatment and uses simplistic theories that anyone can “understand”. But, in doing so, the industry takes advantage of a patient’s vulnerability.

It’s easy to blame your condition on toxic chemicals and unnatural sources. It’s hard to admit that sometimes your body needs outside “unnatural” help in the battle against a disease, especially if it’s a battle you’re losing. But if you broke your leg, you would get it fixed. Internal “breakages” also need medical intervention.

 

Conclusions

 

What is my conclusion? Listen to your doctor. They are trained in treating human diseases and disorders; in fact, they have dedicated their lives to it. Talk to them about your concerns. If they dismiss them, then speak with them more: it’s their job to listen to you. Nowadays medicine is more patient-focussed and doctors should be willing to work with their patients. Doctors will be able to determine where a homeopathic treatment may be appropriate for you, as in the above cases.

If your condition is beyond help with conventional methods, by all means homeopathy may help you. If your conviction is strong enough that a placebo is sufficient, try homeopathy. But really nowadays homeopathic treatment is best alongside conventional medicine: there’s a reason it’s sometimes called complementary medicine.

If you want to try homeopathic treatment, just make sure it’s from a reputable source, and that it’s safe.

 

 

Postscript:

This blog is my opinion only, and it is largely my personal exploration of homeopathy as a treatment. In the case of X-rays, I have compacted an extremely large amount of information into a short space, so please do have a further look at the literature if you are interested! In particular, I would recommend the book “Strange Glow: The Story of Radiation” by Timothy Jorgensen.

Also, I am aware that I did only one calculation for the homeopathic remedies. So here is another, for fun:

 

Homepathic remedy:

Alium cepa (red onion)

160 g, 3X potency, £22.35

3X potency is 1 in 103

This is 0.16 g onion in the 160 g

Each tablet is 0.11 g; so, per tablet, we are looking at 0.00011 g of onion

 

Tesco medium red onion:

1 onion (according to tesco.com) is £0.16, about 220 g

The amount in one tablet is therefore one two millionth of an onion.

The mark up for this remedy is therefore 19,000,000%.

And another, as requested:

Homepathic remedy: Weleda Sulphur 30c 125 Tablets

125 tablets, at £0.05 per 100 mg tablet
30C potency is 1 in 100 to the power of 30
This is 1 x 10^-61 g of sulphur in each tablet

– Please note that the mass of a proton (the smallest chemical element) is 1 x 10^-23 g. This is less than that. This means that, in one tablet of this stuff, there is not even one atom of sulphur present.

Sulphur from Sigma-Aldrich (chemical company):

This is £26.50 for 1 kg.
The mark up for this remedy is 2.65 x 10^64 %. Which is 265 with 62 zeroes after it %.

References:

  1. Tim Minchin’s song, Storm: https://www.youtube.com/watch?v=KtYkyB35zkk
  2. British Homeopathic Association Website, accessed 19/06/16: http://www.britishhomeopathic.org/
  3. The Society of Homeopaths’ Website, accessed 19/06/16: http://www.homeopathy-soh.org/
  4. Science and Technology Committee evidence check on homeopathy, 8th February 2010: http://www.publications.parliament.uk/pa/cm200910/cmselect/cmsctech/45/4502.htm
  5. Homeopathy on NHS choices, accessed 19/06/16: http://www.nhs.uk/conditions/homeopathy/pages/introduction.aspx
  6. Nice article on the use of X-rays in radiation treatment: http://www.pbs.org/newshour/updates/emil-grubbe-first-use-radiation-treat-breast-cancer/
  7. The evolution of cancer treatments: Radiation, accessed 19/06/16: http://www.cancer.org/cancer/cancerbasics/thehistoryofcancer/the-history-of-cancer-cancer-treatment-radiation
  8. Hay fever on NHS choices, accessed 19/06/16: http://www.nhs.uk/Conditions/Hay-fever/Pages/Introduction.aspx
  9. Hay Fever on Allergy UK, accessed 19/06/16: https://www.allergyuk.org/hayfever-and-allergic-rhinitis/hay-fever-and-allergic-rhinitis
  10. Kim LS, Riedlinger JE, Baldwin CM, Hilli L, Khalsa SV, Messer SA, Waters RF (2005). Treatment of seasonal allergic rhinitis using homeopathic preparation of common allergens in the southwest region of the US: a randomized, controlled clinical trial. Annals of Pharmacotherapy; 39:617–624.
  11. Reilly DT, Taylor MA, McSharry C, Aitchison T (1986). Is homeopathy a placebo response? Controlled trial of homeopathic potency, with pollen in hayfever as model. Lancet; ii: 881–885.
  12. Homeopathic preparations, Wikipedia, accessed 19/06/16: https://en.wikipedia.org/wiki/Homeopathy#Preparations_and_treatment
  13. Mercury(I) chloride on Sigma-Aldrich: http://www.sigmaaldrich.com/catalog/product/sial/230405?lang=en&region=GB
  14. Helios homeopathy shop, accessed 19/06/16: https://www.helios.co.uk/shop/mercurius-dulcis
  15. Water purification standards, accessed 19/06/16: http://www.anglianwater.co.uk/_assets/media/Standards_Current.pdf or  http://dwi.defra.gov.uk/consumers/advice-leaflets/standards.pdf

Pharmacogenomics & Personalised Medicine

As promised – here is the second post of two to begin my hopefully-more-regular posting of blog posts!

As a change of pace from the “Problems in Pharmacology” series of posts, I thought it would be good to provide a solution. Pharmacogenomics is a merging of pharmacology and genetics, wherein genetic information from the patient can be used to determine their response to a drug.

Personalised medicine is a proposed method of healthcare that involves tailoring a patient treatment to that patient. This seems like a no-brainer: surely every form of healthcare should be personalised? However, in order for healthcare to be fully personalised, we must use pharmacogenomics. Conventional medicine treats a patient’s symptoms, and perhaps biomarkers (such as chemicals found in their fluid samples), with therapeutic drugs known to reduce these signs, and therefore likely the disease the patient has.

The current healthcare system is reactive, requiring evident symptoms to treat conditions, and thus blocks innovation and inherently finds it tricky to treat conditions with little to no symptoms. The future of healthcare therefore lies in treating the mechanisms of disease, based on evidence found inside the patient.

In order to obtain this “evidence” professionals need to be have genome-based training, and we must integrate the technology necessary into our healthcare system. Instead of looking for symptoms, we should also look at a patient’s risk factors – factors which would enable the development of risk patterns for understanding the various differing diseases leading to a patient’s condition.

Unfortunately these steps are extremely costly: it’s unlikely we’ll get to these stages in the near future. But changes in thinking could do a lot to enhance our current understanding of medicine.

We can’t get data from everyone – but we should understand that we don’t know everything about a patient, and that their condition is dynamic.
Incidental findings are not anomalous – they are misunderstood.

Hopefully a paradigm shift from the treatment of “common complex diseases” to “multiple rare diseases” would help medical professionals and researchers to fully acknowledge the depth of complexity in even our common diseases.
Cliché though it may be, we can paraphrase Socrates in this issue: The only thing that we know is that we know nothing.

This post is entirely my own opinion, based on my own experiences – feel free to disagree and share your thoughts in the comments!

 

A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 4 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

Problems in Pharmacology: Data Collection and Consent

After an extended hiatus, I decided to do two quick posts to sum up some the most contested general issues in current pharmacology. Firstly: data collection and ethics.

In order to overcome some of the boundaries faced by the modern doctor, it is essential that they have access to data and private information regarding the condition and treatments of other patients. It therefore follows that, in order to fully examine research into future treatments of human diseases, pharmacological researchers should also have access to a certain amount of data – at least to avoid them wasting their time or making the same mistakes as doctors in the past.

Resized

Patient data obtained in the hospital is extremely delicately handled. As someone who has personally dealt with this data, I’ll lay it out in a basic form below.

The first step is obtaining consent, in every situation. This means that a researcher must outline all possible uses for a patient’s samples and obtain the patient’s permission.

This consent form must be stored indefinitely in a fashion that anonymises it. This may be through filing certain personal data in a form, then making that form inaccessible to the researchers so that they might only refer to the patient as “patient x” for example.

This data is kept so that, in the future, an authorised person may go back to it and cross-reference any particular qualities the patient may have (their age for example) against other relevant patients to determine whether these qualities may have any effect on their condition. Anonymisation means that researchers have access only to information relevant to their work and not to any other information – their address, for example. Complete anonymisation is difficult, however.

Ways around this consent issue could be use of cell lines (cells cultured from known sources) or the use of samples from deceased patients. However, the latter still does require consent, and the former is only appropriate for certain kinds of research. Clinical pharmacological research requires clinical samples (such as saliva, urine) from living patients. Therefore researchers very much appreciate consenting patients – they really do help a lot!

A lot of useful data is also found in Biobanks (such as: http://www.ukbiobank.ac.uk ). These Biobanks collect relevant samples (blood, urine, saliva) from patients, which allows them to follow the health of these patients. This allows the generation of a database following the treatment of patients with a vast range of diseases: cancer, stroke, diabetes, arthritis, the list goes on!

Why, you might ask, are these banks not used universally then? The issue is simply: ethics.

Different countries require different forms of ethical approval and data processing. In order for data exchange between authorities worldwide, there must be a worldwide ethical framework.

In addition to these issues, there is another at the forefront of research worldwide: procurement and exchange of genetic information. To fully understand many conditions (especially those most prevalent such as cancer and heart disease) it may be necessary to examine the genetics of a patient. There would therefore need to be a consensus between not only biobanks but genetic databases as well.

The future of this research thus requires streamlining of the process of consent, and a greater understanding in patients of what giving consent really can achieve.

This post is entirely my own opinion, based on my own experiences – feel free to disagree and share your thoughts in the comments! Please also note that I have only extremely briefly summarised the process of consent and anonymisation above for the sake of space and tedium!

 

A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 4 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

Problems in Pharmacology: Clinical Trials and Molecular Markers

This week’s post follows on from something I touched on last week: the issues in the drug design process.

Drug design tends to be stem either from mimicry of molecules the chemist knows that the drug target already interacts with (such as a substrate that binds to an enzyme) or from knowledge of the potential’s drug target’s structure (where computer modelling, for example, can suggest which would be the best structure for a potential drug).Resized

These drugs are synthesized, and then undergo preclinical testing. This involves assessment of their stability and their interaction with an isolated drug target (called in vitro testing), and then testing inside animal models. After these stages, totalling up to 6 years, the drug will go to clinical trials in patients.

Clinical trials are in three stages, with the amount of patients in each stage increasing as confidence in the drug’s capabilities develops. The final stages are then approval by the authorities and marketing. This drug discovery process takes in total anything between 10 and 16 years and will cost the company up to a billion dollars. And yet, there are still issues with drug safety that slip through the net: think of thalidomide as the most popular example! Why is this?

There are a multitude of reasons of course. Once a drug has reached later trials, a company can become invested in it and wish to push it through. There may also be signs that the drug is unsafe missed, which may come from the design of the clinical trial itself.

In clinical pharmacology, a biomarker is a characteristic the patient has that can be measured during clinical trials, and is used as an indicator of their biological state. For example, a biomarker such as glucose or hormone levels can indicate the likelihood that a patient will get better or relapse.

A key issue with clinical trials is that they do not measure all relevant biomarkers. A different drug for the same medical condition will have a different action (mechanism) in the body and therefore will have a different effect on biomarkers. They may effect biomarkers that were unaffected by other drugs.

Therefore, in order to fully understand the effect of the drug in the body and truly assess its safety, trials should be randomised with controls (patients taking “placebo” pills with no drug in them to show how biomarkers might change with no drug present). The system currently unfortunately relies on the validation of biomarkers to display patient health, which is both a lengthy and difficult process.

New clinical trial designs are therefore being considered, such as the “I-SPY 2” trial which uses molecular tests to tailor treatment or “BATTLE” which uses biomarkers to tailor the treatment. These new designs are quite new, so unfortunately I am unable to provide more detail than this!

The future of drug discovery seems to be tending towards the more in silico side of research, which uses computational modelling of drug action to suggest how a drug will act in a given system. The future looks bright here, but again that is a discussion for a later post!

I based this post on a talk at the EACPT 2013 conference by Professor Max Parmar (UCL). This post is entirely my own opinion, based on my own experiences – feel free to disagree and share your thoughts in the comments! I’ll be continuing on the “Problems in Pharmacology” theme next week!

 

A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 4 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

Problems in Pharmacology: Definitions and crossing the Biology/Chemistry Border

I thought a good way to begin this blog was with a series of posts dedicated to defining what exactly pharmacology is, and the inherent difficulties in studying  and practicing it. First of all: definitions!

Chemistry is the study of the composition, properties and behaviour of matter, whilst biology is the study of life and living organisms.Resized

Pharmacology is a boundary science, by which I mean it lies firmly on the border of chemistry and biology, dabbling in both but not really studied by scientists within either of these disciplines. Broadly speaking, pharmacology is the science associated with the study of drug action within a living organism.

And therein lies the problem: in order to truly be a pharmacologist, one must not only understand the structure of a drug, one must also be able to ascertain all interactions with the patient’s cells and biological molecules. This is really, really hard.

As a chemistry student, I have also taken modules in biology. The issue with studying biology as a chemist is that modules designed for chemists differ greatly from those the biologists study – imagine the chemistry student looking through a soundproof viewing window into a biology lecture, unable to hear the words, but being able to see some of the diagrams, and given a description of them by a chemist standing next to them.

It is much the same in biology – having taken modules in the life sciences, chemical subjects are approached as though the subject matter should inherently be treated as alien. Unfortunately, at undergraduate level at least, this is unavoidable.

Students on three or four year courses cannot entirely straddle two departments, where lecture modules later on usually depend on some understanding of several modules taken in earlier years. There is just not enough time to learn every module needed, unless a student decides to specialise in a boundary science at the very onset of their degree. This appears to be a massive commitment, which I personally did not wish to make at the age of 18.

These degrees, such as biochemistry, do not tend to entirely cross the boundary either, they tend to be taught predominantly in one department or the other. Chemistry and biology teaching methods require different learning styles. Having done a variety of these modules myself, I find it awkward to switch between the chemistry style of understanding of process and the biology style of memorising definitions and mechanisms.

As the depth of our understanding in these disciplines increases, such boundaries may only widen. But this is not necessarily a bad thing – it is simply a product of progress, which in science is always good!

Though at undergraduate level it may seem that biology and chemistry are miles apart, upon reaching research level this is not so. More and more research groups contain both biologist and chemist specialists, who may benefit from each other’s knowledge. Many universities recognise chemical biology modules as an essential part of a chemist’s degree, more in silico (computation) research focuses on interaction of proteins and enzymes, and more of the more specific areas of chemistry are opening up to biomedical application.

This is a promising start to widening study of pharmacology and other boundary sciences, but it is not the end. Pharmacology in particular seems to be a specialist science studied mainly in hospitals by clinicians.

Picture1Because the science relies on clinical trials (or in silico research, which I’ll discuss later), it is often overlooked by academic researchers and undergraduates. Although pharmacological research would, ideally, be implemented into the earlier stages of drug design, it is often carried out reactively rather than pre-emptively. I think I’ll leave this discussion for now, though: pharmacology in drug design could fill an entire post by itself!

I feel that a solution to undergraduates being underexposed to the more specific areas of chemistry and biology would be to have lecture series for active researchers just to discuss their specific disciplines. Of course, this sounds very basic, and it is! Different universities tend to churn out scientists specialising in the area the university department itself tends to specialise in. Exposing their students to other areas of research could lead to more well-rounded researchers with a greater understanding of the scientific world as a whole.

This post is entirely my own opinion, based on my own experiences – feel free to disagree and share your thoughts in the comments!

 

A note from the author: As my posts sometimes touch on emotive subjects, comments are disabled after 4 days. This is because, at this stage, I feel that ongoing discussions tend to stagnate.

Hello world!

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Hello world!

This is my first post, so a perfect opportunity to just let you know what to expect from this blog. The reason I decided to ask for a blog here? Why not? It’s a good place to keep my interests in scientific topics other than my Masters project, to record and summarise them.

I am currently studying for to be a Master of Chemistry in Chemical Biology – meaning that I am constantly torn between the two vast academic worlds of chemistry and biology, and I love them both.

Posts here will largely lie at the border of these two disciplines, and in pharmacology (the science of drugs in the body). Firstly I’ll be writing on interesting snippets of conferences I’ve been to, but who knows what else may pop up! Let me know if there’s any topics or news stories you think I would be interested in.

My first proper post will be up at the end of the week. I plan to do a post at least weekly :).